Free-Breathing Phase-Resolved Oxygen-Enhanced Pulmonary MRI Based on 3D Stack-of-Stars UTE Sequence.

Compared with hyperpolarized noble gas MRI, oxygen-enhanced lung imaging is a cost-effective approach to investigate lung function. In this study, we investigated the feasibility of free-breathing phase-resolved oxygen-enhanced pulmonary MRI based on a 3D stack-of-stars ultra-short echo time (UTE) sequence. We conducted both computer simulation and in vivo experiments and calculated percent signal enhancement maps of four different respiratory phases on four healthy volunteers from the end of expiration to the end of inspiration. The phantom experiment was implemented to verify simulation results. The respiratory phase was segmented based on the extracted respiratory signal and sliding window reconstruction, providing phase-resolved pulmonary MRI. Demons registration algorithm was applied to compensate for respiratory motion. The mean percent signal enhancement of the average phase increases from anterior to posterior region, matching previous literature. More details of pulmonary tissues were observed on post-oxygen inhalation images through the phase-resolved technique. Phase-resolved UTE pulmonary MRI shows the potential as a valuable method for oxygen-enhanced MRI that enables the investigation of lung ventilation on middle states of the respiratory cycle.

Identification of suitable reference genes for real-time quantitative PCR analysis of hydrogen peroxide-treated human umbilical vein endothelial cells.

BACKGROUND: Oxidative stress can induce cell injury in vascular endothelial cells, which is the initial event in the development of atherosclerosis. Although quantitative real-time polymerase chain reaction (qRT-PCR) has been widely used in gene expression studies in oxidative stress injuries, using carefully validated reference genes has not received sufficient attention in related studies. The objective of this study, therefore, was to select a set of stably expressed reference genes for use in qRT-PCR normalization in oxidative stress injuries in human umbilical vein endothelial cells (HUVECs) induced by hydrogen peroxide (H2O2). RESULTS: Using geNorm analysis, we found that five stably expressed reference genes were sufficient for normalization in qRT-PCR analysis in HUVECs treated with H2O2. Genes with the most stable expression according to geNorm were U6, TFRC, RPLP0, GAPDH, and ACTB, and according to NormFinder were ALAS1, TFRC, U6, GAPDH, and ACTB. CONCLUSION: Taken together, our study demonstrated that the expression stability of reference genes may differ according to the statistical program used. U6, TFRC, RPLP0, GAPDH, and ACTB was the optimal set of reference genes for studies on gene expression performed by qRT-PCR assays in HUVECs under oxidative stress study.

MicroRNA-210 Modulates the Cellular Energy Metabolism Shift During H2O2-Induced Oxidative Stress by Repressing ISCU in H9c2 Cardiomyocytes.

BACKGROUND/AIMS: The myocardial energy metabolism shift is one of the most important pathological features of ischemic heart disease (IHD). Although several microRNAs (miRs) are involved in the regulation of myocardial energy metabolism, their exact effects and underlying mechanisms remain unclear. The aim of this study was to investigate whether microRNA(miR-210) regulates the energy metabolism shift during oxidative stress in H9c2 cardiomyocytes. METHODS: Cell survival was analyzed via CCK assay. The energy metabolism shift was detected by lactate assay, ATP assay and RT2 profiler glucose metabolism PCR array. Protein and mRNA expression levels were determined by western blot and qPCR. We also used kits to detect the activity of Complex I, Sirt3 and the NAD+/NADH ratio. RESULTS: We determined that miR-210 promoted the energy metabolism shift. The iron-sulfur cluster assembly protein (ISCU) was a target of miR-210. Additionally, we detected the activity of complex I and found that miR-210 inhibits mitochondrial respiration. Interestingly, miR-210 may also indirectly regulate SIRT3 by regulating ISCU. CONCLUSION: Our results confirm that miR-210 is essential and sufficient for modulating the cellular energy metabolism shift during H2O2-induced oxidative stress in H9c2 cardiomyocytes by targeting ISCU.

[Quantitative evaluation of inhibitory effects of epileptic spikes on theta rhythms in the network of hippocampal CA3 and entorhinal cortex in patients with temporal lobe epilepsy].

Epileptic spike is an indicator of hyper-excitability and hyper-synchrony in the neural networks. The inhibitory effects of spikes on theta rhythms (4-8 Hz) might be helpful to understand the mechanism of epileptic damage on the cognitive functions. To quantitatively evaluate the inhibitory effects of spikes on theta rhythms, intracerebral electroencephalogram (EEG) recordings with both sporadic spikes (SSs) and spike-free transient period between adjacent spikes were selected in 4 patients in the status of rapid eyes movement (REM) sleep with temporal lobe epilepsy (TLE) under the pre-surgical monitoring. The electrodes of hippocampal CA3 and entorhinal cortex (EC) were employed, since CA3 and EC built up one of key loops to investigate cognition and epilepsy. These SSs occurred only in CA3, only in EC, or in both CA3 and EC synchronously. Theta power was respectively estimated around SSs and during the spike-free transient period by Gabor wavelet transform and Hilbert transform. The intermittent extent was then estimated to represent for the loss of theta rhythms during the spike-free transient period. The following findings were obtained: (1) The prominent rhythms were in theta frequency band; (2) The spikes could transiently reduce theta power, and the inhibitory effect was severer around SSs in both CA3 and EC synchronously than that around either SSs only in EC or SSs only in CA3; (3) During the spike-free transient period, theta rhythms were interrupted with the intermittent theta rhythms left and theta power level continued dropping, implying the inhibitory effect was sustained. Additionally, the intermittent extent of theta rhythms was converged to the inhibitory extent around SSs; (4) The average theta power level during the spike-free transient period might not be in line with the inhibitory extent of theta rhythms around SSs. It was concluded that the SSs had negative effects on theta rhythms transiently and directly, the inhibitory effects aroused by SSs sustained during the spike-free transient period and were directly related to the intermittent extent. It was indicated that the loss of theta rhythms might qualify exactly the sustained inhibitory effects on theta rhythms aroused by spikes in EEG. The work provided an argumentation about the relationship between the transient negative impact of interictal spike and the loss of theta rhythms during spike-free activity for the first time, offered an intuitive methodology to estimate the inhibitory effect of spikes by EEG, and might be helpful to the analysis of EEG rhythms based on local field potentials (LFPs) in deep brain.

Diagnostic Value of Serum YKL-40 Level for Coronary Artery Disease: A Meta-Analysis.

OBJECTIVE: This meta-analysis aimed to identify the value of serum YKL-40 level for the diagnosis of coronary artery disease (CAD). METHODS: Through searching the following electronic databases: the Cochrane Library Database (Issue 12, 2013), Web of Science (1945 ∼ 2013), PubMed (1966 ∼ 2013), CINAHL (1982 ∼ 2013), EMBASE (1980 ∼ 2013), and the Chinese Biomedical Database (CBM; 1982 ∼ 2013), related articles were determined without any language restrictions. STATA statistical software (Version 12.0, Stata Corporation, College Station, TX) was chosen to deal with statistical data. Standard mean difference (SMD) and its corresponding 95% confidence interval (95% CI) were calculated. RESULTS: Eleven clinical case-control studies that recruited 1,175 CAD patients and 1,261 healthy controls were selected for statistical analysis. The main findings of our meta-analysis showed that serum YKL-40 level in CAD patients was significantly higher than that in control subjects (SMD = 2.79, 95% CI = 1.73 ∼ 3.85, P < 0.001). Ethnicity-stratified analysis indicated a higher serum YKL-40 level in CAD patients than control subjects among China, Korea, and Denmark populations (China: SMD = 2.97, 95% CI = 1.21 ∼ 4.74, P = 0.001; Korea: SMD = 0.66, 95% CI = 0.17 ∼ 1.15, P = 0.008; Denmark: SMD = 1.85, 95% CI = 1.42 ∼ 2.29, P < 0.001; respectively), but not in Turkey (SMD = 4.52, 95% CI = -2.87 ∼ 11.91, P = 0.231). CONCLUSION: The present meta-analysis suggests that an elevated serum YKL-40 level may be used as a promising diagnostic tool for early identification of CAD.

Anti-apoptotic effect of microRNA-30b in early phase of rat myocardial ischemia-reperfusion injury model.

This study aimed to investigate the effect of microRNA-30b (miR-30b) in rat myocardial ischemic-reperfusion (I/R) injury model. We randomly divided Sprague-Dawley (SD) rats (n = 80) into five groups: 1) control group; 2) miR-30b group; 3) sham-operated group; 4) I/R group, and 5) I/R+miR-30b group. Real-time quantitative polymerase chain reaction, immunohistochemical staining and Western blot analysis were conducted. TUNEL assay was employed for testing cardiomyocyte apoptosis. Our results showed that miR-30b levels were down-regulated in I/R group and I/R + miR-30b group compared with sham-operated group (both P < 0.05). However, miR-30b level in I/R + miR-30b group was higher than I/R group (P < 0.05). Markedly, the apoptotic rate in I/R group showed highest in I/R group (P < 0.05). Additionally, the results illustrated that protein levels of Bcl-2, Bax, and caspase-3 were at higher levels in ischemic regions in I/R group, comparing to sham-operated group (all P < 0.05), while Bcl-2/Bax was reduced (P < 0.05). Bcl-2 level and Bcl-2/Bax were obviously increased in I/R + miR-30b group by comparison with I/R group, and expression levels of Bax and caspase-3 were down-regulated (all P < 0.05). We also found that in I/R + miR-30b group, KRAS level was apparently lower and p-AKT level was higher by comparing with I/R group (both P < 0.05). Our study indicated that miR-30b overexpression had anti-apoptotic effect on early phase of rat myocardial ischemia injury model through targeting KRAS and activating the Ras/Akt pathway.

The protective effect of microRNA-320 on left ventricular remodeling after myocardial ischemia-reperfusion injury in the rat model.

The primary objective of this study investigated the role of microRNA-320 (miR-320) on left ventricular remodeling in the rat model of myocardial ischemia-reperfusion (I/R) injury, and we intended to explore the myocardial mechanism of miR-320-mediated myocardium protection. We collected 120 male Wistar rats (240-280 g) in this study and then randomly divided them into three groups: (1) sham surgery group (sham group: n=40); (2) ischemia-reperfusion model group (I/R group: n=40); and (3) I/R model with antagomir-320 group (I/R+antagomir-320 group: n=40). Value changes of heart function in transesophageal echocardiography were recorded at various time points (day 1, day 3, day 7, day 15 and day 30) after surgery in each group. Myocardial sections were stained with hematoxylin and eosin (H&E) and examined with optical microscope. The degree of myocardial fibrosis was assessed by Sirius Red staining. Terminal dUTP nick end-labeling (TUNEL) and qRT-PCR methods were used to measure the apoptosis rate and to determine the miR-320 expression levels in myocardial tissues. Transesophageal echocardiography showed that the values of left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP) and ±dp/dtmax in the I/R group were obviously lower than those in the sham group, while the left ventricular end-diastolic pressure (LVEDP) value was higher than that in the sham group. The values of LVEF, LVFS, LVSP and ±dp/dtmax showed a gradual decrease in the I/R group, while the LVEDP value showed an up tendency along with the extension of reperfusion time. The H&E staining revealed that rat myocardial tissue in the I/R group presented extensive myocardial damage; for the I/R+antagomir-320 group, however, the degree of damage in myocardial cells was obviously better than that of the I/R group. The Sirius Red staining results showed that the degree of myocardial fibrosis in the I/R group was more severe along with the extension of the time of reperfusion. For the I/R+antagomir-320 group, the degree of myocardial fibrosis was less severe than that in the I/R group. Tissues samples in both the sham and I/R+antagomir-320 groups showed a lower apoptosis rate compared to I/R group. The qRT-PCR results indicated that miR-320 expression in the I/R group was significantly higher than that in both the sham and I/R+antagomir-320 groups. The expression level of miR-320 is significantly up-regulated in the rat model of myocardial I/R injury, and it may be implicated in the prevention of myocardial I/R injury-triggered left ventricular remodeling.

Electrochemical Visualization of Single-Molecule Thiol Substitution with Nanopore Measurement.

Reactions involving sulfhydryl groups play a critical role in maintaining the structure and function of proteins. However, traditional mechanistic studies have mainly focused on reaction rates and the efficiency in bulk solutions. Herein, we have designed a cysteine-mutated nanopore as a biological protein nanoreactor for electrochemical visualization of the thiol substitute reaction. Statistical analysis of characteristic current signals shows that the apparent reaction rate at the single-molecule level in this confined nanoreactor reached 1400 times higher than that observed in bulk solution. This substantial acceleration of thiol substitution reactions within the nanopore offers promising opportunities for advancing the design and optimization of micro/nanoreactors. Moreover, our results could shed light on the understanding of sulfhydryl reactions and the thiol-involved signal transduction mechanisms in biological systems.

[Comparison study of endobronchial ultrasound-guided transbronchial needle aspiration and transbronchial needle aspiration for the diagnosis of hilar and mediastinal lesions].

OBJECTIVE: To compare the values of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and TBNA for the diagnosis of hilar and mediastinal lesions. METHODS: The clinical data of 100 patients who underwent EBUS-TBNA (n=50) and TBNA (n=50) between January 2010 and May 2011 were retrospectively reviewed, and the results and complications were recorded. RESULTS: A total of 121 lesions in the 100 patients were evaluated, the sample yeilds of EBUS-TBNA and TBNA were 90.6% and 78.9% and the diagnostic accuracy rates in the two groups were 90.0% and 72.0%(P=0.022), respectively. No major complications happened. The sensitivity, specificity and accuracy of EBUS-TBNA were higher and the complication rate was not increased as compared with TBNA. CONCLUSION: EBUS-TBNA has a higher diagnostic yield for the evaluation of hilar and mediastinal lesions.

A Soft Label Method for Medical Image Segmentation with Multirater Annotations.

In medical image analysis, collecting multiple annotations from different clinical raters is a typical practice to mitigate possible diagnostic errors. For such multirater labels' learning problems, in addition to majority voting, it is a common practice to use soft labels in the form of full-probability distributions obtained by averaging raters as ground truth to train the model, which benefits from uncertainty contained in soft labels. However, the potential information contained in soft labels is rarely studied, which may be the key to improving the performance of medical image segmentation with multirater annotations. In this work, we aim to improve soft label methods by leveraging interpretable information from multiraters. Considering that mis-segmentation occurs in areas with weak supervision of annotations and high difficulty of images, we propose to reduce the reliance on local uncertain soft labels and increase the focus on image features. Therefore, we introduce local self-ensembling learning with consistency regularization, forcing the model to concentrate more on features rather than annotations, especially in regions with high uncertainty measured by the pixelwise interclass variance. Furthermore, we utilize a label smoothing technique to flatten each rater's annotation, alleviating overconfidence of structural edges in annotations. Without introducing additional parameters, our method improves the accuracy of the soft label baseline by 4.2% and 2.7% on a synthetic dataset and a fundus dataset, respectively. In addition, quantitative comparisons show that our method consistently outperforms existing multirater strategies as well as state-of-the-art methods. This work provides a simple yet effective solution for the widespread multirater label segmentation problems in clinical diagnosis.

Biomaterials-mediated targeted therapeutics of myocardial ischemia-reperfusion injury.

Reperfusion therapy is widely used to treat acute myocardial infarction. However, its efficacy is limited by myocardial ischemia-reperfusion injury (MIRI), which occurs paradoxically due to the reperfusion therapy and contributes to the high mortality rate of acute myocardial infarction. Systemic administration of drugs, such as antioxidant and anti-inflammatory agents, to reduce MIRI is often ineffective due to the inadequate release at the pathological sites. Functional biomaterials are being developed to optimize the use of drugs by improving their targetability and bioavailability and reducing side effects, such as gastrointestinal irritation, thrombocytopenia, and liver damage. This review provides an overview of controlled drug delivery biomaterials for treating MIRI by triggering antioxidation, calcium ion overload inhibition, and/or inflammation regulation mechanisms and discusses the challenges and potential applications of these treatments clinically.

Leveraging non-expert crowdsourcing to segment the optic cup and disc of multicolor fundus images.

Multicolor scanning laser imaging (MCI) images have broad application potential in the diagnosis of fundus diseases such as glaucoma. However, the performance level of automatic aided diagnosis systems based on MCI images is limited by the lack of high-quality annotations of numerous images. Producing annotations for vast amounts of MCI images will be a prolonged process if we only employ experts. Therefore, we consider non-expert crowdsourcing, which is an alternative approach to produce useful annotations efficiently and low cost. In this work, we aim to explore the effectiveness of non-expert crowdsourcing on the segmentation of the optic cup (OC) and optic disc (OD), which is an upstream task for glaucoma diagnosis, using MCI images. To this end, desensitized MCI images are independently annotated by four non-expert annotators, constructing a crowdsourcing dataset. To profit from crowdsourcing, we propose a model consisting of coupled regularization network and segmentation network. The regularization network generates learnable pixel-wise confusion matrices (CMs) that reflects preferences of each annotator. During training, the CMs and segmentation network are simultaneously optimized to enable dynamic trade-offs for non-expert annotations and generate reliable predictions. Crowdsourcing learning using our method have an average Mean Intersection Over Union ( M ) of 91.34%, while the average M of model trained by expert annotations is 91.72%. In addition, comparative experiments show that in our segmentation task non-expert crowdsourcing can be on a par with the expert who annotates 90% of data. Our work suggests that crowdsourcing in the segmentation of OC and OD using MCI images has the potential to be a substitute to expert annotation, which will accelerate the construction of large datasets to facilitate the application of deep learning in clinical diagnosis using MCI images.

Comparison of effectiveness and safety of high-power vs. conventional-power radiofrequency ablation for treatment of atrial fibrillation.

Aim: To compare high-power (HP) vs. conventional-power (CP) radiofrequency ablation for atrial fibrillation (AF). Methods: We retrospectively enrolled AF patients undergoing CP (30-40 W, 43 patients) or HP (50 W, 49 patients) radiofrequency ablation. Immediate pulmonary vein (PV) single-circle isolation, PV-ablation time, AF recurrence, AF recurrence-free survival, and complications were analyzed. Results: Diabetes was more common in the CP group than in the HP group (27.91% vs. 10.20%, P = 0.029). The left PV single-circle isolation rate (62.79% vs. 65.31%), right PV single-circle isolation rate (48.84% vs. 53.06%), and bilateral PV single-circle isolation rate (32.56% vs. 38.78%; all P > 0.05) did not differ between the groups. Single-circle ablation times for the left PVs (12.79 ± 3.39 vs. 22.94 ± 6.39 min), right PVs (12.18 ± 3.46 vs. 20.67 ± 5.44 min), and all PVs (25.85 ± 6.04 vs. 45.66 ± 11.11 min; all P < 0.001) were shorter in the HP group. Atrial fibrillation recurrence within 3 months (13.95% vs. 18.37%), at 3 months (11.63% vs. 8.16%), and at 6 months after ablation (18.60% vs. 12.24%; all P > 0.05) was similar in both groups. Atrial fibrillation recurrence-free survival did not differ between the groups (Kaplan-Meier analysis). Cardiac rupture and pericardial tamponade did not occur in any patient. Pops occurred in 2 and 0 patients in the HP and CP groups, respectively (4.08% vs. 0.00%, P = 0.533). Conclusion: High-power ablation improved operation time and efficiency without increasing complications.

Long Noncoding RNAs in Myocardial Ischemia-Reperfusion Injury.

Following an acute myocardial infarction, reperfusion therapy is currently the most effective way to save the ischemic myocardium; however, restoring blood flow may lead to a myocardial ischemia-reperfusion injury (MIRI). Recent studies have confirmed that long-chain noncoding RNAs (LncRNAs) play important roles in the pathophysiology of MIRIs. These LncRNA-mediated roles include cardiomyocyte apoptosis, autophagy, necrosis, oxidative stress, inflammation, mitochondrial dysfunction, and calcium overload, which are regulated through the expression of target genes. Thus, LncRNAs may be used as clinical diagnostic markers and therapeutic targets to treat or prevent MIRI. This review evaluates the research on LncRNAs involved in MIRIs and provides new ideas for preventing and treating this type of injury.

Immobilization of Glycogen Synthase Kinase-3ß Inhibitor on 316L Stainless Steel via Polydopamine to Accelerate Endothelialization.

The coverage of stents with healthy endothelium is crucial to the success of cardiovascular stent implantation. Immobilizing bioactive molecules on stents is an effective strategy to generate such stents. Glycogen synthase kinase-3ß inhibitor (GSKi) is a bioactive molecule that can effectively accelerate vascular endothelialization. In this work, GSKi was covalently conjugated on 316L stainless steel through polydopamine to develop a stable bioactive surface. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and water contact angle results revealed the successful introduction of GSKi onto 316L stainless steel. The GSKi coating did not obviously affect the hemocompatibility of plates. The adhesion and proliferation of human coronary artery endothelial cells (HCAECs) on stainless steel was significantly promoted by the addition of GSKi. In summary, this work provides a universal and stable strategy of immobilizing GSKi on the stent surface. This method has the potential for widespread application in the modification of vascular stents.

Krill and salp faecal pellets contribute equally to the carbon flux at the Antarctic Peninsula.

Krill and salps are important for carbon flux in the Southern Ocean, but the extent of their contribution and the consequences of shifts in dominance from krill to salps remain unclear. We present a direct comparison of the contribution of krill and salp faecal pellets (FP) to vertical carbon flux at the Antarctic Peninsula using a combination of sediment traps, FP production, carbon content, microbial degradation, and krill and salp abundances. Salps produce 4-fold more FP carbon than krill, but the FP from both species contribute equally to the carbon flux at 300 m, accounting for 75% of total carbon. Krill FP are exported to 72% to 300 m, while 80% of salp FP are retained in the mixed layer due to fragmentation. Thus, declining krill abundances could lead to decreased carbon flux, indicating that the Antarctic Peninsula could become a less efficient carbon sink for anthropogenic CO2 in future.

Cobalt and nitrogen codoped carbon nanotubes derived from a graphitic C3N4 template as an electrocatalyst for the oxygen reduction reaction.

Sluggish oxygen reduction reaction kinetics have been a main obstacle for commercial application of fuel cells. To replace Pt-based noble metal electrocatalysts, it is crucial to develop economical materials as electrocatalysts. Herein, we provide a strategy to prepare Co and N codoped carbon nanotubes for efficient oxygen reduction reaction. The composites are synthesized by hydrothermal reaction followed by calcination at 900 °C. Graphitic carbon nitride is used as a template and nitrogen source, and citric acid and cobalt nitrate hexahydrate are used as carbon and cobalt sources, respectively. Due to the synergistic effect of Co and N codoping and increased specific surface area, the resulting Co and N codoped carbon nanotubes exhibit excellent catalytic performance. The present results provide experimental support for further development of electrocatalysts.

Mechanisms of lncRNA/microRNA interactions in angiogenesis.

Angiogenesis is a complex physiological process. However, over the past couple of decades, abnormally accelerated or pathological angiogenesis has garnered greater attention from researchers the world over. Studies have shown that this abnormal and uncontrolled angiogenesis not only promotes inflammatory responses but also plays a role in various malignant and cardiovascular diseases. These include solid tumors, atherosclerosis, blinding retinopathy, and other diseases. Furthermore, there is mounting evidence that noncoding RNAs, especially lncRNAs and microRNAs, play important roles in the regulation of angiogenesis. In recent years, numerous studies have found that lncRNA may serve as an endogenous sponge to regulate the expression and function of miRNA, which in turn bind to lncRNA, regulating their stability. Therefore, this review focuses on the mechanisms of lncRNA/microRNA interactions in angiogenesis. A better understanding of such lncRNA/microRNA interactions may provide helpful insights and shed new light on areas of research for identifying diagnostic markers and therapeutic approaches for treating angiogenesis-related diseases.

[Effects of probucol, aspirin and atorvastatin combination therapy upon atherosclerosis].

OBJECTIVE: To investigate the effects of probucol, aspirin and atorvastatin (PAS) combination therapy upon atherosclerosis. METHODS: A total of 436 patients with coronary artery disease were selected and randomly divided into control group (aspirin 100 mg, atorvastatin 10 mg daily) and PAS group (aspirin 100 mg, atorvastatin 10 mg and probucol 0.25 g daily). After a 1-year treatment course, 378 cases remained in the study (201 in control group vs. 177 in PAS group). These patients were followed for throughout the study course and their serum levels of high density lipoprotein (HDL), ox-LDL, TXB2 and MMP-9 were measured at 6 and 12 months respectively. Twenty cases were diagnosed with carotid artery plaque by carotid ultrasound and 16 cases remained in the PAS group. They were followed with ultrasound for plaque thickness. RESULTS: In the control group, the pre-treatment level of MMPs and ox-LDL were not statistically different from the post-treatment level (P > 0.05). In the PAS group, the pre-treatment level of ox-LDL was (23.46 +/- 0.01) mmol/L and the post-treatment level (16.13 +/- 0.02) mmol/L. There was a decrease of 31.7% (P < 0.05). The pre-treatment level of MMPs and MMP-9 in the control group was not statistically different from the post-treatment level. The pre-treatment level of MMP-9 in the PAS group was (7.15 +/- 0.01) mmol/L and the post-treatment level (4.19 +/- 0.02) mmol/L. There was a decrease of 42.4% (P < 0.05). During the course of follow-up, the hospitalization rate, angina recurrence rate, myocardial infarction rate and mortality rate for the control group were 23 (11.4%), 28 (13.9%), 4 (2.0%) and 2 (1.0%) respectively. In the PAS group, the corresponding values were 6 (3.4%), 13 (7.3%), 1 (0.6%) and 0 respectively. All parameters of adverse events showed a significant decrease in the PAS group (P < 0.05). Among the cases with carotid plaque, the pretreatment measurements of intima thickness and plaque thickness were (0.103 +/- 0.002) cm and (0.248 +/- 0.001) cm while the post-treatment corresponding measurements (0.097 +/- 0.001) cm and (0.209 +/- 0.002) cm respectively. There was a significant difference between the PAS group and the control group (P < 0.05). CONCLUSION: Antioxidant probucol significantly inhibits the generation of ox-LDL and MMP-9. PAS therapy also reduces the plaque thickness and decreases the rate of adverse event in patients with atherosclerosis. Antioxidants can be considered as a new adjunct therapy in the treatment of atherosclerosis.

Medullary Respiratory Circuit Is Reorganized by a Seasonally-Induced Program in Preparation for Hibernation.

Deep hibernators go through several cycles of profound drops in body temperature during the winter season, with core temperatures sometimes reaching near freezing. Yet unlike non-hibernating mammals, they can sustain breathing rhythms. The physiological processes that make this possible are still not understood. In this study, we focused on the medullary Ventral Respiratory Column of a facultative hibernator, the Syrian hamster. Using shortened day-lengths, we induced a "winter-adapted" physiological state, which is a prerequisite for hibernation. When recording electrophysiological signals from acute slices in the winter-adapted pre-Bötzinger complex (preBötC), spike trains showed higher spike rates, amplitudes, complexity, as well as higher temperature sensitivity, suggesting an increase in connectivity and/or synaptic strength during the winter season. We further examined action potential waveforms and found that the depolarization integral, as measured by the area under the curve, is selectively enhanced in winter-adapted animals. This suggests that a shift in the ion handling kinetics is also being induced by the winter-adaptation program. RNA sequencing of respiratory pre-motor neurons, followed by gene set enrichment analysis, revealed differential regulation and splicing in structural, synaptic, and ion handling genes. Splice junction analysis suggested that differential exon usage is occurring in a select subset of ion handling subunits (ATP1A3, KCNC3, SCN1B), and synaptic structure genes (SNCB, SNCG, RAB3A). Our findings show that the hamster respiratory center undergoes a seasonally-cued alteration in electrophysiological properties, likely protecting against respiratory failure at low temperatures.